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WMCheerman
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Coivd Moon Shot, alchemical free energy calculations

Hello every one, I noticed that Folding@Home announced today that they are running "alchemical free energy calculations," I was curious if this is similar to Auto Dock? On that note someone with better understanding of these projects then me, what are the differences of the Covid moon shot Project and what Scripps is doing here on WCG?
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Jim1348
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Re: Coivd Moon Shot, alchemical free energy calculations

If you look at the link provided by Bruce (the moderator at Folding) to my question, you will know a bit more about how Folding and Docking relate. But I am not an expert on the subject, and what Scripps is doing here is a bit more than just "docking".
https://foldingforum.org/viewtopic.php?f=17&t=35110#p336603
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[Edit 2 times, last edit by Jim1348 at Jul 28, 2020 8:39:44 PM]
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WMCheerman
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Re: Coivd Moon Shot, alchemical free energy calculations

Wow, thanks for the information! Could you elaborate more on what you meant by Scripps is doing more then Docking?
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Jim1348
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Re: Coivd Moon Shot, alchemical free energy calculations

Could you elaborate more on what you meant by Scripps is doing more then Docking?

Docking method: Reactive docking (Giulia)
The main innovation of our approach resides in the docking protocols we are using. Together with conventional dockings, in which we try to predict which molecules can bind transiently (i.e., reversibly) on the protein surface, we are using a new protocol, called ‘reactive docking’, to find irreversible binders: molecules that can bind tighter and irreversibly. One of the advantages of this class of molecules is that once they latch on their target, they disable it until the protein is degraded, which is clearly a great feature to have in a drug! and if properly designed they can be very selective.
https://forlilab.org/opn-update-7-20/
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hnapel
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Re: Coivd Moon Shot, alchemical free energy calculations

... ‘reactive docking’, to find irreversible binders: molecules that can bind tighter and irreversibly. ...
https://forlilab.org/opn-update-7-20/


This is also referred as covalent bonds, in fact you are making a new molecule, that of the protein and the compound which will hopefully monkey wrench the function of the target protein.
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hnapel
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Re: Coivd Moon Shot, alchemical free energy calculations

What Fornilab is doing on WCG and John Chodera etc. on F@H is ultimately quite similar: test compounds against viral protein targets to see if they may be turned into viable drugs. What I gather is Openpandemics is screening large libraries of molecules + some hypotethical compounds that could be made from existing ones relatively easy (ask a chemist...). The covid moonshot project is different in that all potential candidates are engineered up-front with the idea that they might work, the molecules are designed by collaborators that may have a good intuition or otherwise for compounds that will fit the viral protein targets. Also since they are not existing molecules, they work on creating chemical routes for compounds that are calculated on volunteer computers to be promising and then to make them for actual testing in a biolab.
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Jim1348
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Re: Coivd Moon Shot, alchemical free energy calculations

That is as good a summary and comparison as I have seen. I have no idea which is more likely to get there first, but it is important to develop both if only for the next virus to come along.
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